The present invention relates to a liquid chromatograph, and more particularly to a liquid chromatograph having a miniaturized analytical section for separation and detection of a small amount of sample.
The present invention also relates to a sample introduction apparatus and method suitable for a microliquid chromatograph by using a capillary column as a separation column.
The present invention is also concerned with a detector disposed in a liquid chromatograph for detecting ionic components contained in a liquid sample to be analyzed, and more particularly with a liquid chromatograph detector which is inexpensive and disposable.
In a conventional chromatograph, a carrier liquid delivery section, a sample injection section, a separation column, a detector and the like are provided independently of each other and these sections are connected through conduits. However, with such a structure, it is necessary to solve a variety of technical difficulties in order to miniaturize the analyzer.
For example, since the separation column is composed of a micro bore glass tube having an inner diameter of 0.1 mm or less, the glass tube is fragile and it would be difficult to perform a line connection with other elements and to handle the glass tube.
Also, a dead volume of fittings or connectors would be increased to a level not neglibible in comparison with a capacity of the separation column, so that it would be difficult to enhance a performance, a precision and a reproducibility of the separation and detection of the components contained in the sample.
There has also been provided a conventional apparatus in which a sample injection valve and a detector are directly connected to a separation column in order to reduce a dead volume, for example, in Journal of Chromatographic Science, Vol. 21, July 1983, pp. 326-330, in particular, FIGS. 2 and 3 and the related description. However, even with such an apparatus, it would be difficult to satisfactorily solve the above-described problems.
On the other hand, in a field of gas chromatography, there have been some proposals for miniaturization. For instance, Stephen C. Terry et al., "A Gas Chromatographic Air Analyzer Fabricated on a Silicon Wafer", IEEE, Transactions on Electron Devices, vol. Ed-26, No. 12, December 1979, pp. 1880-1886 shows a gas chromatograph structure in which a capillary column is formed on a silicon substrate and a part of the structure including a detector is integrated. In this publication, there is also a proposal of a method for forming a sample injection valve on the silicon substrate.
Incidentally, Japanese Patent Unexamined Publication No. 61-262659 shows a gas chromatograph in which a thermal conduction detector is disposed on a silicon wafer.
In a liquid chromatograph, in contrast to a gas chromatograph, however, it is necessary to switch over liquid separation flow paths when the sample is introduced into the separation column. It is therefore difficult to miniaturize the analytical section even if the structure of the gas chromatograph proposed in the prior art is applied to the liquid chromatograph without change. Also, the flow path arrangement would be complicated.
More specifically, in case of gas chromatography, the introduction of the sample gas is performed under a pressure (relatively low level) substantially equal to a pressure of the column, whereas, in the case of liquid chromatography, the same method as the gap chromatography can not be used because the pressure in the column should be high. The sample may be injected similarly only when the pressure is 30-40 kgf/cm.sup.2. Thus, a sample valve where the sample has been injected beforehand is provided to allow the sample to be introduced into column when the sample valve is operated or switched over. The liquid chromatograph should have a flow switching-over valve having a high mechanical strength or a separation column having a high mechanical strength which is capable of arranging the mechanically strong switching valve.
A first object of the invention is to provide a liquid chromatograph that is easy to handle in spite of high miniaturization of an analyzer provided with a sample components separation ability.
In addition, the prior art method for forming the sample injection valve on the silicon substrate as shown with reference to gas chromatography is superior in view of the resulting small dead volume, but is disadvantageous because of requirements in a complicated structure, complicated manufacture, steps, and means for liquid-tight seal under high pressure required for liquid chromatography.
A second object of the present invention is provide a sample introduction apparatus for a capillary liquid chromatograph which is simple in structure and easy to manufacture, and to provide a method therefor.
Furthermore, according to the conventional technique proposed in the above-mentioned literature by Stephen C. Terry et al., since the thermal conductivity detector which is effective only on a gas sample is used, there is a problem that a liquid sample cannot be analyzed. Moreover, a certain carrier liquid has a high electrical conductivity, and if the liquid sample is brought into direct contact with electrodes of the conventional detector, a noise in an output signal from the detector would be unduly large. Thus, there has been no attempt of applying the conventional electrical conductivity detector to a liquid chromatograph.
In view of the above-described deficiency, the third object of the invention is to provide a liquid chromatograph which is small in size and inexpensive and which is capable of detecting ionic components contained in the liquid sample without fail.